is essential for zebrafish embryogenesis and pronephros formation.

Background And Objectives: Friedreich's Ataxia (FRDA) is a genetic disease that affects a variety of different tissues. The disease is caused by a mutation in the gene ( which is important for the synthesis of iron-sulfur clusters. The primary pathologies of FRDA are loss of motor control and cardiomyopathy.

Emx2 is an essential regulator of ciliated cell development across embryonic tissues.

Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffer's vesicle (KV), which establishes left/right axial pattern. deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), determining that is essential to properly establish several renal lineages.

Using Zebrafish to Study Multiciliated Cell Development and Disease States.

Multiciliated cells (MCCs) serve many important functions, including fluid propulsion and chemo- and mechanosensing. Diseases ranging from rare conditions to the recent COVID-19 global health pandemic have been linked to MCC defects. In recent years, the zebrafish has emerged as a model to investigate the biology of MCCs.

Multiciliated cell development and ciliary resorption at the mammalian choroid plexus.

Ciliopathies are a group of diseases caused by defects in cilia, hair-like organelles that can have many functions ranging from regulating extracellular fluid flow to sensing mechanical or chemical stimuli. Multiciliated cells (MCCs) with motile cilia are found in locations that include the central nervous system, where they are critical for homeostasis. Specifically, ependymal MCCs line the brain ventricles and central canal of the spinal cord, while other specialized MCCs occupy highly vascularized structures known as the choroid plexuses (ChPs) and produce cerebrospinal fluid (CSF).

Estrogen signaling in development: recent insights from the zebrafish.

While traditionally recognized as a sex hormone, estrogen has a potent effect on the development of tissues beyond those of the reproductive system. Estrogen synthesis enzymes and estrogen receptors are broadly expressed in vertebrate tissues, further indicating their importance in various processes. These include the tissues of the zebrafish, which is a particularly suitable model for studying early development due to its rapid ontogeny and conserved genetic and cellular composition with other vertebrates.

One small step for stool, one giant leap for IBD surveillance.

Inflammatory bowel diseases (IBDs) are chronic conditions in which the digestive tract undergoes cycles of relapsing and remitting inflammatory episodes that cause patients to experience severe abdominal pain, bleeding, and diarrhea. Developing noninvasive and cost-effective surveillance methods that can detect an ensuing disease bout proffers an avenue to improve the quality of life for patients with IBD. Now, a recent report describes an ingenious, economical approach using a rationally designed strain that can dynamically monitor inflammation inside the mammalian gastrointestinal tract.

Caught red feathered: infection from cockatoo to human and mice reveals genetic plasticity of during mammalian passage.

The fungus is pervasive in our environment and causes the infectious disease cryptococcosis in humans, most commonly in immunocompromised patients. In addition to corroborating the avian origins of a case of cryptococcosis in an immunocompromised patient in 2000, a fascinating recent report has now characterized the genetic and phenotypic changes that occur in this during passage in mammalian hosts. Interestingly, mouse-passaged isolates showed differences in virulence factors ranging from capsule size, melanization, nonlytic macrophage exocytosis, and amoeba predation resistance as compared to the patient strain.

Tails of nephron ciliated cell development: insights on patterning a functional tissue barrier from the zebrafish.

Cilia are hair-like structures found on the surface of nearly all vertebrate cell types where they have central roles in regulating development and orchestrating physiological events. There is growing interest in understanding the mechanisms of ciliogenesis due to the profound consequences that follow from the absence of proper ciliary function, which include diseases that affect the renal, respiratory, reproductive, nervous, visual, and digestive systems, among others. Now, a recent report has discerned new roles for the transcription factor ( in ciliated cell ontogeny within the embryonic zebrafish kidney and other tissues.

Slow down my beating heart: induction of cardiac fibrosis by Iroquois homeobox 2.

Cardiovascular diseases are a significant global health challenge and pervasive cause of mortality worldwide. Heart failure due to cardiovascular disease is characterized by the inability of the heart to pump blood efficiently to meet the metabolic demands of the body. The pathophysiology of heart failure involves myocardial remodeling due to excessive deposition of extracellular matrix proteins by cardiac myofibroblasts - structural changes which impair contractility, reduce compliance, and ultimately reduce stroke volume.

The amazing axolotl: robust kidney regeneration following acute kidney injury.

The incidence of kidney disease from acute and chronic conditions continues to escalate worldwide. Interventions to replace renal function after organ failure remain limited to dialysis or transplantation, as human kidneys exhibit a limited capacity to repair damaged cells or regenerate new ones. In contrast, animals ranging from flies to fishes and even some mammals like the spiny mouse exhibit innate abilities to regenerate their kidney cells following injury.

Genetic mechanisms of multiciliated cell development: from fate choice to differentiation in zebrafish and other models.

Multiciliated cells (MCCS) form bundles of cilia and their activities are essential for the proper development and physiology of many organ systems. Not surprisingly, defects in MCCs have profound consequences and are associated with numerous disease states. Here, we discuss the current understanding of MCC formation, with a special focus on the genetic and molecular mechanisms of MCC fate choice and differentiation.

Forever young by Alpha(diversity)ville: restricting intestinal microbiome maturation stunts immune system development and increases susceptibility to infection.

The microbiome is a keystone of adult gastrointestinal (GI) tract health, where it facilitates digestion, wards off pathogen colonization, and exerts a powerful influence on the physiological health of organs ranging from the brain to the kidneys. From its establishment at birth and through the initial years of childhood, the human microbiome is particularly dynamic, shifting in its composition and alpha (species) diversity to an adult profile as dietary sustenance transitions from milk-based sources to others such as solid food. An innovative study has now demonstrated how microbiome maturation is requisite both for the progression of immune system development and for long-term gut barrier function.

You shall not pass: how complement C5 mediated antifungal immunity blocks systemic candidiasis and preserves renal tissue barriers.

The rising prevalence of fungal infections is a significant and growing public health threat, and this risk is further underscored by our incomplete understanding of why organs like the kidney are so susceptible to systemic candidiasis. To combat the high mortality of such infections, we urgently need to advance our understanding of fungal pathogenesis and how it articulates with human immune response. Now, a recent landmark study has illuminated a crucial role of the complement system in the response to candidiasis and determined the stepwise local response of phagocytes within the kidney during infection.

Cannabinoid Signaling in Kidney Disease.

Endocannabinoid signaling plays crucial roles in human physiology in the function of multiple systems. The two cannabinoid receptors, CB1 and CB2, are cell membrane proteins that interact with both exogenous and endogenous bioactive lipid ligands, or endocannabinoids. Recent evidence has established that endocannabinoid signaling operates within the human kidney, as well as suggests the important role it plays in multiple renal pathologies.

(Zebra)fishing for nephrogenesis genes.

Kidney disease is a devastating condition affecting millions of people worldwide, where over 100,000 patients in the United States alone remain waiting for a lifesaving organ transplant. Concomitant with a surge in personalized medicine, single-gene mutations, and polygenic risk alleles have been brought to the forefront as core causes of a spectrum of renal disorders. With the increasing prevalence of kidney disease, it is imperative to make substantial strides in the field of kidney genetics.

Esrrγa regulates nephron and ciliary development by controlling prostaglandin synthesis.

Cilia are essential for the ontogeny and function of many tissues, including the kidney. Here, we report that transcription factor ERRγ ortholog estrogen related receptor gamma a (Esrrγa) is essential for renal cell fate choice and ciliogenesis in zebrafish. esrrγa deficiency altered proximodistal nephron patterning, decreased the multiciliated cell populace and disrupted ciliogenesis in the nephron, Kupffer's vesicle and otic vesicle.

Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease.

Retinoic acid (RA) is a metabolite of vitamin A (retinol) that plays various roles in development to influence differentiation, patterning, and organogenesis. RA also serves as a crucial homeostatic regulator in adult tissues. The role of RA and its associated pathways are well conserved from zebrafish to humans in both development and disease.

Principles of Zebrafish Nephron Segment Development.

Nephrons are the functional units which comprise the kidney. Each nephron contains a number of physiologically unique populations of specialized epithelial cells that are organized into discrete domains known as segments. The principles of nephron segment development have been the subject of many studies in recent years.

Visualizing multiciliated cells in the zebrafish.

Ciliated cells serve vital functions in the body ranging from mechano- and chemo-sensing to fluid propulsion. Specialized cells with bundles dozens to hundreds of motile cilia known as multiciliated cells (MCCs) are essential as well, where they direct fluid movement in locations such as the respiratory, central nervous and reproductive systems. Intriguingly, the appearance of MCCs has been noted in the kidney in several disease conditions, but knowledge about their contributions to the pathobiology of these states has remained a mystery.

Estrogen Signaling Influences Nephron Segmentation of the Zebrafish Embryonic Kidney.

Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. 17β-estradiol (E2), which is the dominant form of estrogen in vertebrates, was a particularly interesting hit from this screen.

The "3Ds" of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening.

A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity.

Modeling Podocyte Ontogeny and Podocytopathies with the Zebrafish.

Podocytes are exquisitely fashioned kidney cells that serve an essential role in the process of blood filtration. Congenital malformation or damage to podocytes has dire consequences and initiates a cascade of pathological changes leading to renal disease states known as podocytopathies. In addition, animal models have been integral to discovering the molecular pathways that direct the development of podocytes.

Renal interstitial cells to the rescue.

The ability of the adult zebrafish to replace damaged nephrons in the kidney depends on renal progenitor cells and renal interstitial cells working closely together.

Advances in Understanding the Genetic Mechanisms of Zebrafish Renal Multiciliated Cell Development.

Cilia are microtubule-based organelles that project from the cell surface. In humans and other vertebrates, possession of a single cilium structure enables an assortment of cellular processes ranging from mechanosensation to fluid propulsion and locomotion. Interestingly, cells can possess a single cilium or many more, where so-called multiciliated cells (MCCs) possess apical membrane complexes with several dozen or even hundreds of motile cilia that beat in a coordinated fashion.